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Stroke Research and Treatment
Volume 2011, Article ID 131834, 7 pages
Review Article

Limited Therapeutic Time Windows of Mild-to-Moderate Hypothermia in a Focal Ischemia Model in Rat

1Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305-5327, USA
2Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA 94305-5327, USA

Received 18 January 2011; Revised 8 April 2011; Accepted 2 May 2011

Academic Editor: Fred Colbourne

Copyright © 2011 Heng Zhao and Gary Steinberg. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Although many studies have shown the great potential of induced hypothermia in stroke treatment, we recognize that there are limitations to the protective effects of hypothermia even in the laboratory. Here, we review our experiments on the protective effects of mild-to-moderate hypothermia in rats. Focal ischemia was induced by bilateral common carotid artery (CCA) occlusion for 1 to 2 hours combined with permanent or transient middle cerebral artery (MCA) occlusion. We compared the effects of mild (33C) and moderate (30C) hypothermia, evaluated therapeutic time windows, and studied the underlying mechanisms. On review, our findings revealed that the protective effects of induced mild hypothermia (33C) were limited, and the therapeutic time window of even moderate hypothermia (30C) was very short in our specific models, although this limitation might be due to the relatively brief periods of hypothermia used. In addition, we found that hypothermia reduced brain injury by preserving Akt activity, PTEN phosphorylation and εPKC activity, while inhibiting ROS production, and δPKC activity.